title: The prognostic impact of TGF-β1, fascin, NF-κB and PKC-ζ expression in soft tissue sarcomas.
abstract: OBJECTIVE
  Transforming growth factor-β (TGF-β), fascin, nuclear factor-kappa B (NF-κB) p105, protein-kinase C-zeta (PKC-ζ), partioning-defective protein-6 (Par-6), E-cadherin and vimentin are tumor promoting molecules through mechanisms involved in cell dedifferentiation. In soft tissue sarcomas, their expression profile is poorly defined and their significance is uncertain. We aimed to investigate the prognostic impact of TGF-β1, NF-κB p105, PKC-ζ, Par-6α, E-cadherin and vimentin in non-gastrointestinal stromal tumor soft tissue sarcomas (non-GIST STSs).
  
  
  METHODS
  Tumor samples and clinical data from 249 patients with non-GIST STS were obtained, and tissue microarrays (TMAs) were constructed for each specimen. Immunohistochemistry (IHC) was used to evaluate marker expression in tumor cells.
  
  
  RESULTS
  In univariate analysis, the expression levels of TGF-β1 (P = 0.016), fascin (P = 0.006), NF-κB p105 (P = 0.022) and PKC-ζ, (P = 0.042) were significant indicators for disease specific survival (DSS). In the multivariate analysis, high TGF-β1 expression was an independent negative prognostic factor for DSS (HR = 1.6, 95% CI = 1.1-2.4, P = 0.019) in addition to tumor depth, malignancy grade, metastasis at diagnosis, surgery and positive resection margins.
  
  
  CONCLUSIONS
  Expression of TGF-β1 was significantly associated with aggressive behavior and shorter DSS in non-GIST STSs.
authors.affiliation: Department of Clinical Pathology, University Hospital of Northern Norway, Tromsø, Norway. Andrej.Yurjevic.Valkov@unn.no
authors.forename: Andrej
authors.initials: A
authors.lastname: Valkov
authors.forename: Sveinung W
authors.initials: SW
authors.lastname: Sorbye
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Kilvaer
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.forename: Eivind
authors.initials: E
authors.lastname: Smeland
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D054337:Cell Dedifferentiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D016328:NF-kappa B / Q000378:metabolism*; D009664:Norway / Q000453:epidemiology; D015588:Observer Variation; D011379:Prognosis; D016016:Proportional Hazards Models; D011493:Protein Kinase C / Q000378:metabolism*; D012509:Sarcoma / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D016019:Survival Analysis; D046888:Tissue Array Analysis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D055815:Young Adult; D000099221:Protein Kinase C zeta
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D008840:Microfilament Proteins; D016328:NF-kappa B; D011493:Protein Kinase C; D053773:Transforming Growth Factor beta1; D000099221:Protein Kinase C zeta; C020324:fascin